The G2/M checkpoint pathway of fission yeast arrests cell cycle progression in the presence of DNA damage and unreplicated DNA. The Rad3 kinase plays a critical role in signaling this cell cycle arrest. Genotoxic insults go unrecognized when rad3+ is mutated, and cells attempt to segregate an abnormal genome. In humans, faulty checkpoint control underlies the symptoms of a disease called Ataxia telangiectasia (A-T). The protein mutated in this disease is ATMp, structurally related to Rad3p. A-T patients suffer from a variety of severe symptoms, including a high incidence of cancers, particularly leukemia and lymphomas. Like rad3 cells, A-T cells are acutely sensitive to ionizing radiation and fail to arrest cell cycle progression in the presence of DNA damage. Rad3p and ATMp are PI-3 related kinases. The regulation of this new family of kinases is not well understood. Evidence suggest they become activated following recruitment by specific protein/DNA complexes. The specific aim of this research is to understand the mechanisms regulating Rad3p kinase activity in the G2/M checkpoint pathway of fission yeast. Regulation of Rad3p likely occurs through its association with a protein/DNA complex. This hypothesis will be tested using genetic and biochemical techniques to identify and define this protein complex and test if it associates with DNA.